This invention relates to novel tricyclic fused pyrimidine derivatives useful as medicines
Pyrazolo[3,4-d]pyrimidine derivatives having, among others, analgesic, antiinflammatory and diuretic actions are disclosed in Japanese Unexamined Patent Publication No. 31694/1978, Japanese Unexamined Patent Publication No. 5082/1986 corresponding to EP166054, and those having, among others, an action of ameliorating cerebral dysfunction are disclosed in Japanese Unexamined Patent Publication No. 10788/1988 corresponding to EP237289. While tricyclic fused pyrimidine derivatives, the fused ring formed at 2- and 3-positions of a 3-aminopyrazolo[3,4-d]pyrimidine ring, have been synthesized [cf. EP306185], tricyclic fused pyrimidine derivatives, wherein at least one of the 1and 3-positions is hydrogen or an optionally substituted aralkyl group, are novel compounds which have not been known at all.
On the other hand, adenosine, as one of the important constituents of a living body, plays an important role for appearance, maintenance and control of various physiological functions intra- and extracellularly. More specifically, adenosine displays a variety of physiological actions in most of the organs and tissues, for example inhibition of cerebral function, vasodilation, cardiac depression, renal vasoconstriction, inhibition of platelet aggregation, modulation of insulin secretion, dysfunction of lymphocytes and modulation of renin release. These actions occur via adenosine receptors which are widespread on the surface of cells in a living body [J. W. Daly, J. Med. Chem., 25,(1982), M. Williams et al., Annu. Rep. Med. Chem., 22, 1 (1987), A. J. Bridges et al., Annu. Rep. Med. Chem., 23, 41 (1988)]. Therefore, diseases caused by physiological abnormality due to changes of interaction between adenosine and its receptors occur generally in the neurosecretion system, cardiovascular and gastro-intestinal tract system. Use of an adenosine antagonist inhibiting the interaction between adenosine and its receptors is considered useful for the therapy and prophylaxis of these diseases [M. Williams et al., Pharm. Biochem. & Behavior, 29, 433 (2988)]. Theophylline having an adenosine antagonist activity, for example, has various pharmacological activities including stimulation of the central nervous system and heart muscle, diuretic action and relaxation of smooth muscle, especially bronchial smooth muscle, and has been widely used clinically. In the cerebral tissue, it is considered that, under conditions of hypoxia or when cerebral blood circulation is blocked, adenosine triphosphate (ATP) of a high-energy compound is decreased to increase the adenosine concentration, and the adenosine acts on the adenosine receptor (A.sub.1) on nerve terminals to cause decrease of intracellular cyclic AMP concentration, opening of K.sup.+ channels and reduction of the Ca.sup.2+ influx, resulting in inhibiting the release of cerebral neuro-transmitters such as acetylcholine, noradrenaline, dopamine and serotonin, thus abnormality occurring in cerebral function and metabolism [B. B. Fredholm et al., Trends in Pharm. Sci. 9, 130 (1988)].